The objective of this project is to reduce the late morbidity and mortality of hematopoietic stem cell transplantation. The major determinants of these late complications include treatment-related toxicities, immunodeficiency and chronic graft-versus-host disease (GVHD). To date, 385 stem cell recipients have been followed annually for up to 25 years after transplantation for aplastic anemia and allied hematologic diseases. Among this cohort (including 105 patients currently more than 10 years posttransplant), late complications included: chronic GVHD (n=179), lung disease (n=67), cataracts (n=47), depression (n=46), bone disease (n=35), lithiasis (n=26), secondary neoplasms (n=10), and major or moderate infections (n-1626 episodes). Accordingly, we propose four interrelated specific aims; 1) Monitor late events and complications after stem cell transplantation and determine the dynamics of psychosocial recovery. In addition, patients will participate in studies of the mechanisms of posttransplant lung disease, pediatric growth and development, and secondary malignancies following transplantation; 2) Reduce infections and mortality after unrelated transplantation in a placebo controlled trial of immunoglobulin prophylaxis. Other studies will evaluate new diagnostic and interventive methods to reduce the morbidity of posttransplant cataract and bone disease; 3) Prevent development of chronic GVHD by novel approaches to long-term immunosuppression and early adjunctive therapy of acute GVHD with ultraviolet radiation; 4) Improve treatment of chronic GVHD by evaluating the efficacy of FK-506, thalidomide, rapamycin and mycophenolate mofetil in an integrated series of pilot and Phase III clinical trials. Concern for the late effects of stem cell transplantation is especially important as new disease indications, preparative regimens and stem cell sources are explored. Although overall survival has improved in recent years, investigation of the late morbidity of transplantation is vital for the well-being of the stem cell recipient.